Although considerable information is available as regards biogenic amine synthesis, release, and uptake, little is known about the further metabolism of the aldehydes which result as a consequence of the action of monoamine oxidase on the neuroamines. This is particularly true with regards to that portion of the aldehydes which bind to tissue protein. Since aldehyde binding to tissue protein is increased by drugs of the alcohol-barbiturate classes, it classes it seems possible this binding maay be of consequence in either the CNS depressant effects of these drugs or in the addiction process which developes as a consequence of chronic use of these drugs. The proposed research will compare and contrast the regional and subcellular distribution o aldhydes derived from norepinephrine, dopamine, and serotonin. These comparisons will be made in both in vitro and in vivo systems. The various subcellular fractions will be isolated by differential density gradient centrifugation following either incubation of radiolabelled amine with brain homogenates or after intraventricular injection of radiolabelled amine or intraperitoneal injection of amine precursors. Pargyline pretreatment will serve as a control. Unbound material will be removed either by equilibrium dialysis or by trichloroacetic acid precipitation of tissue protein followed by extensive acid washing. Th@ effects of those drugs which enhance tissue binding on regional and subcellular distribution of binding will be assessed, along with the effects of the addition of p-chloromercuro benzoate, an agent which inactivates sulfhydryl groups. The information obtained will supply preliminary evidence as to the specificity of binding. This specificity may be either to a particular subcellular fraction or to specific macromolecule Information obtainable from studies of subcellular and regional distribution of binding will provide clues as to which cellular processes may be disrupted by aldehydemacromolecule interactions.